Memory Part 3: The Role of the Fornix and Clinical Cases

The fornix is the major white matter outflow tract from the hippocampus, and pathology involving the fornix would be expected to affect memory. Pathologic processes that affect the hippocampal formation and parahippocampal gyrus, including the entorhinal cortex, correlate with specific types of

T he fornix is the major white matter outflow tract from the hippocampus, and pathology involving the fornix would be expected to affect memory. Pathologic processes that affect the hippocampal formation and parahippocampal gyrus, including the entorhinal cortex, correlate with specific types of memory deficits, 1-10 but the clinical consequences of lesions of the fornix have not been emphasized as often. A familiarity with the anatomy and imaging of the fornix helps to anticipate the clinical impact of pathology and treatment that involves this strategic structure.
The fornix, named for its archlike configuration (Figs 1 and 2), is formed from the fimbria, which is the fringelike medial continuation of the alveus that sits on the superior surface of the hippocampus just below the ependymal lining on the floor of the temporal horn of the lateral ventricles (Fig 3). The posterior portion of the fornix, the crus, also forms the posterior medial margin of the lateral ventricles (Fig 4). The crura are joined across the midline by the psalterium (lyre or Harp of David), also called the hippocampal commissure or commissure of the fornix. 11 The body of the fornix is situated at the dome of the fornical archlike configuration and is connected to the inner surface of the corpus callosum via the septum pellucidum ( Fig 5A). This portion of the fornix is situated at the upper margin of the velum interpositum, which is traversed by the internal cerebral veins, and is above the third ventricle but below the body of the lateral ventricles. The foramen of Monro forms the anterior border of the velum interpositum, which is open at its posterior aspect at the position of the pineal gland ( Fig 5B).
The white matter fibers of the columns of the fornix have a more superoinferior orientation, forming the anterior portion of the fornical arch, and are also joined to the posterior margin of the genu of the corpus callosum via the septum pellucidum (Fig 6). At the level of the anterior commissure, the columns of the fornix split, with most of the fibers coursing posterior to the anterior commissure to form the postcommissural fibers that project to the mammillary bodies, while the minority of precommissural fibers run anterior to the anterior commissure to project to the medial prefrontal cortex, nucleus accumbens, and septal nuclei, which are located deep to the medial aspect of the frontal lobes inferior to the rostrum of the corpus callosum. The fornix also sends smaller fibers to the anterior thalamus.
Clinical and experimental data suggest a functional distribution of the fornical fibers. [12][13][14][15][16] The left fornix primarily carries verbal memory information, while the right carries visuospatial memory information (Fig 7). In addition, the medial fornix carries fibers from the caudal hippocampus, which processes exteroceptive signals and integrates object recognition within a spatial context (ie, scene learning). The lateral aspect of the fornix is presumed to carry projections from the more rostral hippocampus, which processes interoceptive signals for emotional and motivational learning and memory (Fig 8).
Knowledge of this anatomy helps to anticipate clinical deficits and surgical risks. Figure 9 shows the imaging of a 23-year-old woman who presented with progressive headaches over a 2-month period. An unusual lesion was noted within the anterior right lateral ventricle, causing some obstruction of the foramen of Monro. More important, the mass impinged on and displaced the columns of the fornices, right more than left. The neurosurgeons were advised about the close proximity of the fornices to the medial margin of the tumor and the risk of memory impairment. The patient underwent an endoscopic subtotal resection, in which the lesion was discovered to be a glioneuronal neoplasm, which was tightly adherent to the fornical columns. On postoperative day 1, the patient experienced new memory deficits with no recall of the surgery or reason for the surgery. Neuropsychological testing months later showed moderately impaired delayed recall of both verbal and visuospatial materials. Figure 10A shows an axial gradient-echo image of a 60-yearold patient who presented with headaches and memory problems. A large collection of blood was noted in the cistern of the velum interpositum, with superior lateral displacement and compression of the body of the fornices. Cerebral angiography did not reveal any cause for the hemorrhage, and the patient was then monitored with serial MR imaging. Figure 10B shows atrophy of the mammillary bodies, left greater than right, 5 months later. The hematoma had significantly diminished in size with time, but         neuropsychological testing showed that the patient had residual memory impairment, verbal more than visuospatial. This is expected given the lateralization of the verbal memory fibers to the left fornix and its greater involvement by the hematoma as reflected in the smaller left mammillary body. Figure 11 shows the initial imaging of a 56-year-old woman who presented with new onset of memory loss. She would often repeat the same question during the appointment with her doctor, not remembering that her question had already been answered. The infiltrating enhancing lesion of her mammillary bodies, including much of the remainder of the hypothalamus demonstrated on the MR imaging examination, proved to be Langerhans cell histiocytosis.
The effort of investigations in the basic neurosciences will continue to expand and deepen our knowledge of the processes that constitute the experience that is memory, and our everyday clinical effort to understand the functional anatomy of the extended hippocampal network that subserves memory is useful to predict the dysfunctional implications of strategically located lesions and enhance the role of the neuroradiolgist in diagnosis and guiding treatment.